[The plasmic translocation and release of high mobility group box chromosomal protein 1 in peripheral blood monocytes of patients with rheumatoid arthritis and the effect of thalidomide].
OBJECTIVE
To investigate the release and intracellular localization of high mobility group box chromosomal protein 1 (HMGB1) in the peripheral blood monocytes of rheumatoid arthritis (RA) patients and the inhibitive effect of thalidomide.


METHODS
19 RA patients and 20 healthy controls were included in the study. Monocytes were separated from peripheral blood with Ficoll density gradient centrifugation. Monocytes were treated with 100 ng/ml tumor necrosis factor alpha (TNFalpha) or 100 ng/ml TNFalpha plus 40 microg/ml thalidomide and grown in an incubator at 37 degrees C with 5% CO2 for 24 hours. The culture supernatants of the monocytes were collected. HMGB1 level in the culture medium was detected with Western blot. In addition, the intracellular localization of HMGB1 in the monocytes was investigated with immunocytochemical analysis.


RESULTS
Without stimulation, the release of HMGB1 protein was significantly increased in the culture supernatants of peripheral blood monocytes from RA patients as compared with that from healthy controls (P < 0.05). TNFalpha (100 ng/ml) did not further increase the release of HMGB1 in the monocytes from the patients with RA. Thalidomide (40 microg/ml) could inhibit the release of HMGB1 in the monocytes from RA patients stimulated with TNFalpha (P < 0.05). In the monocytes from RA patients, HMGB1 was mainly localized in the nucleus. Treatment with TNFalpha (100 ng/ml) for 24 hours resulted in a cytoplasmic translocation of HMGB1, which was inhibited significantly by thalidomide.


CONCLUSIONS
TNFalpha induces the release and cytoplasmic translocation of HMGB1 in the peripheral blood monocytes of RA patients and thalidomide inhibits the release and translocation of HMGB1.
Zuo
Xiao-Xia
XX
Department of Rheumatology and Immunology, Xiang-ya Hospital, Central South University, Changsha 410008, China. susanzuo@hotmail.com
Gong
Yan-Hui
YH
Zhou
Ya-Ou
YO
Luo
Hui
H
Xiao
Xian-Zhong
XZ
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D003469:Culture; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017077:Culture Media, Conditioned; D024243:HMGB1 Protein; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide